Ultrasound-based imaging, delivery, and cellular control

 

The unique gas compartments of gas vesicles (GVs) possess very different material properties from those of normal aqueous tissue. Over the past few years, my colleague and I in the Shapiro lab at Caltech leveraged these properties to repurpose GVs for biological imaging, including the development of GVs as the first reporter genes for ultrasound imaging (Nature 553, 86), the ultrasound imaging of gene expression in mammalian cells (Science 365, 1469), the establishment of GVs as ‘erasable’ MRI contrast agents (Nature Materials 17, 456), and the use of GVs as reporter genes for optical coherence tomography (ACS Nano 14, 7823). In addition, the interaction of GVs with focused ultrasound (FUS) has been explored to enable new directions on cellular control, such as the spatial control of engineered cells by acoustic trapping (bioRxiv, 691105) and acoustic cavitation for controlled release of cellular content (Nature Nano). Notably, all these methods utilize medical imaging or therapeutic modalities that can noninvasively access centimeter-deep tissue. We envision that, just as how fluorescent proteins and optogenetics enable the use of light to study and manipulate specific cellular processes, GVs can open the door to study molecular events in engineered cells in centimeter-deep tissue, an unmet need for biomedical research especially in the field of cell-based therapies.

We recently published a new genetic variant of GVs that is now of the size of a virus, and to our knowledge, these are the smallest stable, free-floating bubbles made to date. Check out these 50-nm GVs and our demonstration of their ability to penetrate into deep tissues in lymph nodes. See “Virus-size ultrasmall bubbles” in the publication tab (http://lulab.rice.edu/#publication): Shen Q, Li Z, Meyer MD, De Guzman MT, Lim JC, Bouchard RR, Lu GJ (2023) 50-nm gas-filled protein nanostructures to enable the access of lymphatic cells by ultrasound technologies. bioRxiv, 2023.06.27.546433 Tweet, LinkedIn.